Host response to the subtilase cytotoxin produced by locus of enterocyte effacement-negative Shiga-toxigenic Escherichia coli |
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Authors: | Hiroyasu Tsutsuki Kohei Ogura Joel Moss Kinnosuke Yahiro |
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Institution: | 1. Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan;2. Advanced Health Care Science Research Unit, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, Japan;3. Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA;4. Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan |
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Abstract: | Shiga-toxigenic Escherichia coli (STEC) is a major bacterium responsible for disease resulting from foodborne infection, including bloody diarrhea and hemolytic uremic syndrome. STEC produces important virulence factors such as Shiga toxin (Stx) 1 and/or 2. In the STEC family, some locus of enterocyte effacement-negative STEC produce two different types of cytotoxins, namely, Stx2 and subtilase cytotoxin (SubAB). The Stx2 and SubAB cytotoxins are structurally similar and composed of one A subunit and pentamer of B subunits. The catalytically active A subunit of SubAB is a subtilase-like serine protease and specifically cleaves an endoplasmic reticulum (ER) chaperone 78-kDa glucose-regulated protein (GRP78/BiP), a monomeric ATPase that is crucial in protein folding and quality control. The B subunit binds to cell surface receptors. SubAB recognizes sialic carbohydrate-modified cell surface proteins as a receptor. After translocation into cells, SubAB is delivered to the ER, where it cleaves GRP78/BiP. SubAB-catalyzed BiP cleavage induces ER stress, which causes various cell events including inhibition of protein synthesis, suppression of nuclear factor-kappa B activation, apoptotic cell death, and stress granules formation. In this review, we describe SubAB, the SubAB receptor, and the mechanism of cell response to the toxin. |
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Keywords: | apoptosis endoplasmic reticulum stress receptor Shiga-toxigenic Escherichia coli subtilase cytotoxin |
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